Platelet granule secretion plays a key role in atherothrombosis. Curcumin, a natural polyphenol compound derived from turmeric, exerts multiple biological activities. The current study sought to investigate the efficacy of tetrahydrocurcumin (THC, the major active metabolite of curcumin) on platelet granule secretion in vitro and thrombus formation in vivo. We found that THC significantly attenuated agonist-induced granule secretion in human gel-filtered platelets in vitro, including CD62P and CD63 expression and platelet factor 4, CCL5, and adenosine triphosphate release. These inhibitory effects of THC were partially mediated by the attenuation of cytosolic phospholipase A₂ (cPLA₂) phosphorylation, leading to a decrease in thromboxane A₂ (TxA₂) generation. Moreover, the MAPK (Erk1/2, JNK1/2, and p38 MAPK) signaling pathways were downregulated by THC treatment, resulting in reduced cPLA₂ activation, TxA₂ generation, and granule secretion. Additionally, THC and curcumin attenuated murine thrombus growth in a FeCl₃-induced mesenteric arteriole thrombosis model in C57BL/6J mice without prolonging the tail bleeding time. THC exerted more potent inhibitory effects on thrombosis formation than curcumin. Through blocking cyclooxygenase-1 activity and thus inhibiting platelet TxA₂ synthesis and granule secretion with aspirin, we found that THC did not further decrease the inhibitory effects of aspirin on thrombosis formation. Thus, through inhibiting MAPKs/cPLA₂ signaling, and attenuating platelet TxA₂ generation, granule secretion, and thrombus formation, THC may be a potent cardioprotective agent.

血小板颗粒分泌在动脉粥样硬化血栓形成中起关键作用。姜黄素是一种从姜黄中提取的天然多酚化合物，具有多种生物活性。目前的研究旨在研究四氢姜黄素（THC，姜黄素的主要活性代谢物）对体外血小板颗粒分泌和体内血栓形成的功效。我们发现 THC 在体外显着减弱了人凝胶过滤血小板中激动剂诱导的颗粒分泌，包括 CD62P 和 CD63 表达以及血小板因子 4、CCL5 和三磷酸腺苷释放。THC 的这些抑制作用部分是通过细胞溶质磷脂酶 A ₂ (cPLA ₂ ) 磷酸化的减弱来介导的，从而导致血栓素 A ₂ (TxA ₂） 一代。此外，MAPK（Erk1/2、JNK1/2 和 p38 MAPK）信号通路被 THC 处理下调，导致 cPLA ₂激活、TxA ₂生成和颗粒分泌减少。_{此外，THC 和姜黄素在 C57BL/6J 小鼠的 FeCl 3}诱导的肠系膜小动脉血栓形成模型中减弱了鼠血栓的生长，而没有延长尾部出血时间。THC 对血栓形成的抑制作用比姜黄素更强。通过阻断环氧合酶-1 活性从而抑制血小板 TxA ₂合成和阿司匹林颗粒分泌，我们发现 THC 并未进一步降低阿司匹林对血栓形成的抑制作用。因此，通过抑制 MAPKs/cPLA ₂TxA ₂的生成、颗粒分泌和血栓形成，THC 可能是一种有效的心脏保护剂。